This proposal seeks funding for the purchase of an integrated Finnigan ion-trap mass spectrometer system. This system includes the new second generation LC1/DECA ion trap mass spectrometer, a ternary gradient narrow-bore HPLC/MS system with a UV6000 diode array detector and TSP autosampler. Additional hardware accessories are requested including a low-volume flow cell for the HPLC diode array detector and three separate probes that operate with the standard electro spray source: a nanoprobe (for status and dynamic nanospray), an off-axis electro spray probe, and an atmospheric pressure chemical ionization (APCI) probe. In addition, four separate software add-ons are requested including a Discovery software package (CombiChem software), a BioWorks package (SEAQUEST, Biotools, and deconvolution software), Max Frontier mass spectrometric interpretation software (chemical drawing, fragmentation predictions and automated MS assignment) and a second copy of the operating Xcalibur software for remote second-site data analysis. We propose to operate this instrument in three modes: 1) off- line MS/n with capabilities up to n=10 for detailed structural characterization of complex carbohydrates, modified peptides and selected small molecules, 2) on-line HPLC-MS and HPLC-MS/MS for complex mixtures analysis including peptides, carbohydrates, receptor ligands and the more complex synthetic libraries, and 3) automated high- throughput drug or compound screening (HTDS) of synthetic combinatorial libraries. The primary users consists of two major groups of independent researchers The first group consists of Dr. Gibson (carbohydrate and protein chemistry/mass spectrometry applied to studies of bacterial carbohydrates in disease), Dr. I.D. Kuntz (a leading theoretical-computational chemist in the area of drug design) and Dr. Susan Fischer (a biomedical research in the area of glycoproteins and preeclampsia). The second group of investigators are involved in the general area of synthetic organic chemistry and is headed by Dr. Tom Scanlan (targeting nuclear and peptide ligand receptor interaction), along with Dr. Kip Guy (combinatorial synthesis, protein-protein interactions and drug effects on gene expression) and Dr. Matthew Bogyo (protein discovery via synthetic peptide-ligands containing reactive electrophiles).